PRODUCT CHARACTERIZATION AND PRECLINICAL SAFETY OF UMBILICAL CORD MESENCHYMAL STROMAL CELL-DERIVED SMALL EXTRACELLULAR VESICLES

Mesenchymal stromal cells (MSCs) are multipotent progenitors that can be isolated from different sources, such as the bone marrow, adipose tissue and umbilical cord. The therapeutic potential of MSCs is related to a plethora of immunomodulatory, anti-inflammatory and pro-repair actions, which are at least partially dependent on their secretome. Among the components of MSCs' secretome, EVs have received considerable attention because MSC-EVs exert similar therapeutic properties as their parent cells. Among the different MSC sources for EV production, human umbilical cord MSCs (hUCMSCs) show advantages such as tissue availability, high proliferative profile of the cells and potential beneficial therapeutic effects in a variety of different diseases, such as stroke This study aimed to provide novel insights for future hUCMSC-EVs research and treatment selection. We investigated the influence of the culture and harvesting conditions on the EV proteomic profile, productivity, surface markers expression and evaluated their in vivo biodistribution and toxicity.

间充质基质细胞（Mesenchymal Stromal Cells, MSCs）是一类多能祖细胞，可从骨髓、脂肪组织、脐带等多种组织来源中分离获取。MSCs的治疗潜力与其广泛的免疫调节、抗炎及促修复作用密切相关，这些功能至少部分依赖于其分泌组（secretome）。在MSCs分泌组的各类组分中，细胞外囊泡（Extracellular Vesicles, EVs）受到了广泛关注，因为MSC来源的EVs与其亲本细胞具有相似的治疗特性。在可用于生产EV的多种MSC来源中，人脐带间充质干细胞（human umbilical cord MSCs, hUCMSCs）具备诸多优势：组织获取便捷、细胞增殖活性高，且对脑卒中等多种不同疾病均具有潜在的有益治疗效果。本研究旨在为未来hUCMSC-EVs的相关研究与治疗方案选择提供全新视角。我们探究了培养与收获条件对EV蛋白质组学特征、产量及表面标志物表达的影响，并评估了其体内生物分布与毒性。